A bipartite structural organization defines the SERINC family of HIV-1 restriction factorsMore about Open Access at the Crick
Authors listVal Pye Annachiara Rosa Cinzia Bertelli Weston B Struwe Sarah L Maslen Robin Corey Idlir Liko Mark Hassall Giada Mattiuzzo Allison Ballandras-Colas Andrea Nans Yasuhiro Takeuchi Phillip J Stansfeld Mark Skehel Carol V Robinson Massimo Pizzato Peter Cherepanov
The human integral membrane protein SERINC5 potently restricts HIV-1 infectivity and sensitizes the virus to antibody-mediated neutralization. Here, using cryo-EM, we determine the structures of human SERINC5 and its orthologue from Drosophila melanogaster at subnanometer and near-atomic resolution, respectively. The structures reveal a novel fold comprised of ten transmembrane helices organized into two subdomains and bisected by a long diagonal helix. A lipid binding groove and clusters of conserved residues highlight potential functional sites. A structure-based mutagenesis scan identified surface-exposed regions and the interface between the subdomains of SERINC5 as critical for HIV-1-restriction activity. The same regions are also important for viral sensitization to neutralizing antibodies, directly linking the antiviral activity of SERINC5 with remodeling of the HIV-1 envelope glycoprotein.
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